Transcript Ocular Pathology

Wendy Chen, MD, PhD: PGY-3
Charleen T. Chu, MD, PhD: Neuropathology

50 yo Caucasian male presenting with right
lower eyelid erythema and thickening.
 Itchy
 Erythema fluctuates, worse after sun exposure
 No change in vision
 Some AM eyelid matting/crusting

Seen by dermatologist in 2006 -- bilateral
periorbital rash, erythematous and itchy,
scaling plaques, worsened by sun exposure.

? Rosacea ---> treated with Akne-mycin
(erythromycin 2%) without improvement.
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Punch biopsy of LEFT lower eyelid
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Dermatopathology report:
“lichenoid dermatitis with deep perivascular
extension of the infiltrate . . . lupus
erythematosis vs. lichenoid photodermatitis”
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Subsequently,
 PAS stain: thickened basement membrane
 Colloidal iron: focal increase in dermal mucin
 Favoring discoid lupus erythematosis

Treated with Protopic (tacrolimus 0.1%) –
bilateral periorbital rash improved.

Serologic testing:
 ANA, RF, Anti-DNA, Anti-histone, Anti-SS A/B
negative.
 C3, C4 WNL
 CBC, LFTs, BMP WNL
 RPR non-reactive

Over the next 3 years, pt continued to have
intermittent flares of periorbital, facial, and
scalp rashes ---> continued Protopic.
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In 2009, presented to dermatology again with
persistent RLL erythema and thickening
accompanied by erythematous pustules of
the face ---> acne rosacea

To ophthalmology for second opinion
Past Medical/Surgical History
• Acne rosacea
• Lupus erythematosis,
DISCOID, not systemic
• Anxiety, Depression
• S/P hernia repair
Past Ocular History
• S/P left periorbital skin bx
• Hyperopia
• Astigmatism
Social History
• Tob – none
• EtOH – social use
• Drugs – none
• Excessive sun exposure
and multiple severe
sunburns prior to age 18
Medications
Topical tacrolimus 0.1% prn
Lexapro
Ativan
Va CC:
Pupils:
IOP:
EOM:
CVF:
20/20 OU
No APD
14 OU
Full OU
Full OU
OD
OS
External
Acne rosacea
Acne rosacea
Lids/Lashes
LL with MGD, telangiectasia,
diffuse erythema and thickening,
no distortion of lash line or
madarosis
Normal
Conj/Sclera
White and quiet
White and quiet
Cornea
Clear
Clear
AC
Deep and quiet
Deep and quiet
Iris
Round and reactive
Round and reactive
Lens
Clear
Clear
Vitreous
Normal
Normal

Ocular rosacea – typically bilateral, but can be
asymmetric.

Discoid lupus without systemic involvement.

Infectious – viral, bacterial, fungal.

Malignancy – basal cell carcinoma, squamous
cell carcinoma, sebaceous adenocarcinoma.

Rosacea-associated blepharitis --->
Blephamide BID with resolution of
symptoms.

Returned 5 months later with RLL recurrence
(slow return of symptoms).

Referred to oculoplastics for biopsy.

Wedge resection of lateral portion of the RLL
lesion in Oct 2009.
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Conjunctival cultures taken:
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Fungus culture negative
Virus culture negative
Bacterial culture with light coag neg Staph
Adenovirus PCR negative
HSV1/2 PCR negative
Hyperkeratosis
Acanthosis
Squamous cell nests and strands infiltrating the dermis
Infiltrative border
Suggestion of early keratin pearl formation
Mitotic figures
Interface dermatitis with vacuolar degeneration

EYELID RIGHT LOWER, WEDGE BIOPSY
 A. SUPERFICIALLY INVASIVE SQUAMOUS CELL
CARCINOMA (0.2 CM, 0.1 CM
THICK), WELL DIFFERENTIATED
 NO ANGIOLYMPHATIC OR PERINEURAL
INVASION PRESENT.
 MARGINS FREE OF TUMOR.

Pt continued to have persistent RLL
erythema and thickening.

Re-excision of adjacent area performed Nov.
2009, given prior diagnosis ---> suture with
foreign body giant cell reaction, acute and
chronic inflammation and fibrosis.

Started po Doxycycline 100mg daily for
further treatment of ocular rosacea.

Patient was followed q4 months for 1 yr with
waxing and waning progression of RLL lesion.

Most recent visit revealed a change in
appearance of RLL.
Prior biopsy site
Vertical extension of
the lesion with minor
distortion of lid
architecture

Given the recent change in the appearance of
the lesion and prior diagnosis of carcinoma, a
repeat wedge resection was performed in
January 2011 on the medial portion of the
RLL lesion.
Dense interface dermatitis,
architectural distortion.
Keratin pearl
Maturation & narrow strand-like extensions
suggest pseudocarcinomatous hyperplasia
Thick basement membrane

Review of initial wedge excision revealed that
the diagnosis of carcinoma may have been
incorrect.
 Prolonged clinical history of rashes, chronic
inflammation and suspicion of DLE were not
known to the original pathologist.

Both excisions showed:
 SQUAMOPROLIFERATIVE LESIONS WITH
PSEUDOEPITHELIOMATOUS HYPERPLASIA.
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10-40X less common than basal cell carcinoma.
Typically arise from actinic keratoses.
Lower eyelid most common ocular site.
Histologic characteristics:
 Hyperkeratosis, acanthosis
 Interface dermatitis, infiltrative nests and strands
 Keratinocyte nuclear hyperchromasia and
maturational ayptia, mitotic figures
 Keratin pearls, dyskeratotic cells


Chronic inflammation can result in histologic
changes that mimic invasive squamous
carcinoma.
Features that can help differentiate PCH/PEH
from SCC:
 Narrow, strand-like infiltration of epithelium
▪ Tangential section can result in isolation from surface
 Lack of dysplastic hyperchromatic nuclei, lack of
maturational atypia
▪ Reactive atypia – pale nuclei with uniform nucleoli

Systemic lupus more commonly causes
corneal lesions, retinal vasculopathy
 keratoconjunctivitis sicca, peripheral ulcerative
keratitis, interstitial keratitis


Very rarely can give isolated lid lesions that
mimic malignancy
CCL variants
 Discoid lupus erythematosis – plaque lesions
 Lupus erythematosis profundus (panniculitis)
 Systemic disease - idiopathic orbital edema
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Unlike regular pseudoepitheliomatous
hyperplasia, significant cytologic atypia (N/C
ratio, hyperchromasia, mitoses) can occur.
Features that help differentiate DLE from SCC:
 History of chronicity, rashes
▪ SCC shows rapid onset/growth (< 6 mo), nodular or
ulcerative changes.
 Intradermal mucin (colloidal iron)
 Thickened basement membrane (PAS)
Papalas et al. “Cutaneous Lupus Erythematosus of the Eyelid as a Mimic of
Squamous Epithelial Malignancies” Ophthal Plast Reconstr Surg 2010.

Features that help differentiate CCL from SCC:
 Perifollicular and acrosyringeal inflammation
 Follicular plugging
 Vacuolar interface change
 Compact orthokeratosis
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The “helpful” features may not be present or may not
be recognized without a high index of suspicion
 37% of cutaneous LE cases incorrectly interpreted initially
even by Board certified dermatopathologists
Zedek et al. “Cutaneous Lupus Erythematosis simulating squamous
neoplasia: The clinicopathologic conundrum and histopathologic pitfalls”
J Am Acad Dermatol 2007; 56: 1013-20.
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Persistent unilateral lower lid erythema/thickening
despite treatment of discoid lupus and ocular
rosacea warrants biopsy.
 SCC can develop in lesions of discoid LE
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The histologic DDx includes actinic keratosis/SCC,
lichen planus-like keratosis & PCH/PEH
▪ Combination of cytologic atypia from lupus and PCH/PEH (which
normally lacks atypia) is a diagnostic pitfall
▪ Chronic history and suspicion of lupus would raise the awareness
threshold to prevent overcalling the lesion

Providing clinical history is key to avoiding
misdiagnosis >> rare mimics of a common neoplasm